Which are the causes of Glutaryl-CoA dehydrogenase deficiency / Glutaric aciduria type 1?

Glutaryl-CoA dehydrogenase deficiency, also known as Glutaric aciduria type 1, is a rare genetic disorder that affects the body's ability to break down certain amino acids. This condition is caused by mutations in the GCDH gene, which provides instructions for producing an enzyme called glutaryl-CoA dehydrogenase.

Glutaryl-CoA dehydrogenase is responsible for breaking down the amino acids lysine, hydroxylysine, and tryptophan. When this enzyme is deficient or nonfunctional, these amino acids and their byproducts can build up to toxic levels in the body.

The exact cause of the GCDH gene mutations is not fully understood. However, it is believed to be an autosomal recessive disorder, meaning that an affected individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. If both parents are carriers of the mutated gene, each of their children has a 25% chance of inheriting two copies and developing the disorder.

Glutaryl-CoA dehydrogenase deficiency primarily affects the central nervous system, particularly the basal ganglia, which is responsible for coordinating movement. The accumulation of toxic substances in the brain can lead to neurological damage and the characteristic symptoms of the disorder.

Environmental factors can also play a role in the development and severity of symptoms. It has been observed that certain triggers, such as fever, infections, or prolonged fasting, can worsen the symptoms or lead to acute episodes of metabolic decompensation in affected individuals.

Early diagnosis and treatment are crucial in managing glutaryl-CoA dehydrogenase deficiency. Newborn screening programs can detect elevated levels of certain metabolites in the blood, allowing for early intervention. Treatment typically involves a low-lysine diet supplemented with carnitine and avoidance of fasting. In severe cases, additional therapies such as physical and occupational therapy may be necessary to manage the neurological symptoms.

In conclusion, glutaryl-CoA dehydrogenase deficiency is caused by mutations in the GCDH gene, leading to a deficiency of the enzyme responsible for breaking down specific amino acids. The exact cause of these gene mutations is not fully understood, but it is believed to be an autosomal recessive disorder. Environmental factors can also influence the severity of symptoms. Early diagnosis and intervention are crucial in managing this rare genetic disorder.